The objectives are to provide a better understanding of the anatomy, physiology and biochemistry of the "gastric mucosal barrier" and to elucidate those factors which influence the ability of the mucosa to protect itself against ulceration. A new conceptualization of the barrier as a dynamic phenomenon dependent upon many functional variables has recently been evolved in our laboratory replacing the previous older formulation of a fixed anatomical or physiological gate. In these proposed studies particular emphasis will be placed on testing the capacity of the mucosa to cope with noxious substances, especially H ion in relation to the functional and acid-basis status of the mucosa. An attempt will be made to separate the function of the surface and the oxyntic cells. The role of CO2 and carbonic anhydrase will also be evaluated. Similar aspects of duodenal and jejunal disposal of H ion will be examined. The studies will be carried out both in vitro and in vivo. In vitro, the basic preparation will consist of isolated bullfrog or Necturus antrum or fundus in an Ussing chamber in which P.D., resistance, Isc, H ion or HCO3 negative ion production, and CO2 release can be measured. Attempts will be made to measure intracellular P.D. and pH. In vivo, a specially prepared flap of canine antral or fundic mucosa to which blood flow and blood pressure can be varied will be used to assess the effects of controlled changes in these parameters and in the functional state of the mucosa upon the ability of the mucosa to dispose of H ion. Isolated pouches of antrum and fundus in intact animals will also be used. Finally, an ongoing trial of antacid therapy in the prevention of stress ulcers in man will be carried to completion.